ABSTRACT Acute kidney injury (AKI) is a syndrome characterized by rapid loss of the kidney's excretory function. AKI is the leading cause of nephrology consultation and results in 17 million hospital admissions a year. The socioeconomic impact of AKI is significant, resulting in $10 billion cost to the health care system. Despite the high rate of incidence of AKI, no therapy currently exists, other than supportive care. Also, AKI occurs in up to 30% of all patients undergoing cardiac surgery. Despite advances in bypass techniques and intensive care, mortality and morbidity associated with AKI have not changed in the last decade. Furthermore, AKI represents a potential link to chronic kidney disease. Mesenchymal stem cell (MSC) therapies have shown promise in renal disease models; however, there are logistical barriers and potential safety concerns which will limit the usefulness of this therapy. We and others have shown the therapeutic potential of MSC secretome in ischemia/reperfusion (acute) kidney injury models. Here, we propose to assess the therapeutic effect of NFx-101 (our lead therapeutic agent) in the rat kidney ischemia/reperfusion injury model when infused before, immediately after, or 24-hours post injury as well as to evaluate the therapeutic effect of NFx-101 to prevent development of chronic kidney injury in a rat model of high salt induced kidney failure. As a result of this Phase I study we will establish the optimal NFx- 101 dose and regiment of treatment, which then will be used for Phase II study.